Project Summary Significance: Neuroscientists have set ambitious goals for electrophysiology and stimulation technology but these tools continue to lag behind. The mission is to achieve a scale at least on the order of the local neural circuits and to do so with a technology that does damage this circuit. For decades, one of our best tools has been silicon because of the enormous infrastructure and capabilities centered around this substrate material. Indeed, one of the impressive tools in recent years is the NeuroPixel probe made at a world-class foundry, IMEC. The sheer scale of recording electrodes will certainly be high-impact for acute recording in the brain, however, some damage to the local circuitry is known to exist from the rigidity of silicon. Thus neurotechnologists must also strive to solve the scaling challenge with other materials and add more modalities than recording alone. Critically, the field needs to understand long-term changes in local circuits if we are to fully understand learning, memory, plasticity, and the progression of many disease models. The proposed approach is to achieve the density of local brain regions in a novel platform ? one capable of recording, stimulation, and specifically engineered to achieve reduced mechanical mismatch so a stable circuit interface exists for many months. We propose an unprecedented scale of micro-LEDs and recording electrodes on an ultra-flexible polymer substrate. Neuron-sized lithographically-defined and monolithically- integrated LEDs will allow scalable high-density stimulation, and a flexible substrate will allow the array to float with tissue. Furthermore, the opportunity for this platform to move beyond the brain into the entire nervous system is exciting. Silicon probes are rarely if ever used to study the spinal cord, ganglia, or nerves directly but we think by solving the substrate issue we can finally offer neuroscientists an important way to holistically study brain and body. Preliminary Data: Our previous work has demonstrated the feasibility of GaN-on-silicon optoelectrodes and most recently we prototyped the monolithic integration of GaN LEDs and parylene-C. Separately we have demonstrated the light artifact seen in silicon is primarily from the substrate itself, which is another exciting reason to move away from silicon into thinner, flexible polymer substrates. Specific Aims: In aim 1 we will develop a robust micro-LED optoelectrode on parylene-C. In aim 2, novel micro LED driver, area-efficient low-noise amplifiers, and a new packaging scheme will enable these devices to be used by more neuroscientists at scale. In aim 3, validation of the proposed optoelectrodes will be carried out in longitudinal studies tracking many neurons in a behavior task while being directly compared to a silicon device. In total, this approach should deliver an improved platform and the much needed evidence that our technology is truly moving toward large-scale circuit interfacing.